The psychological stress of bereavement, job insecurity, marital problems, and so forth, have been implicated as risk factors in cardiac sudden death. Our challenge has been to determine the higher cerebral mechanisms by which psychologically and physically stressful stimuli regulate the heart. Previous studies in our laboratory used tone-shock conditioning as the experimental model by which to investigate the effects of the two types of stress on cardiac responses. Electrophysiological recordings of extracellular slow potentials in response to the tone and shock stimuli and functional neural blockade, which abolished these responses as well as the conditioned cardiac response, have together delimited a cerebral system mediating the process. Current work is directed toward understanding the neurochemical transactions in the system (e.g. synaptic transmitters, intracellular mediators, etc.). Specifially we have found, using a new method of cryogenic fixation in vivo, that psychological and physical stress both reduce 3', 5'-adenosine monophosphate levels in parietal cortex. Slow potentials also evoked by the stressful stimuli were found to have a negative correlation (r equals -O.77, p less than or equal to .01) with the cyclic nucleotide level during the development of the response. Cryogenic blockade in the system was found to prevent the onset of ventricular filbrillation following coronary artery occlusion. BIBLIOGRAPHIC REFERENCES: Skinner, J.E. and Yingling, C.D. Central gating mechanisms that regulate event-related potentials and behavior: A neural model for attention. In J.E. Desmedt (Ed.), Progress in Clinical Neurophysiology. Karger, Basel, 1977. Vol. 1, pp 30-69. Yingling, C.D. and Skinner, J.E. Gating of thalamic input to cerebral cortex by nucleus reticularis thalami. In J.E. Desmedt (Ed), Progress in Clinical Neurophysiology. Karger, Basel, 1977. Vol. 1, pp 70-96.